A mGlu2/3 agonist in the treatment of PTSD

谷氨酸能系统在创伤后应激的某些常见行为表现中起作用 精神障碍(PTSD)，例如恐惧学习和焦虑唤醒的机制。我们建议评估这种药物的疗效。 MGlu2/3受体激动剂甲硫氨蝶呤治疗创伤后应激障碍的随机、双盲、 安慰剂对照，II期临床试验。此试验的关键终点包括结构化诊断和自我 报告创伤后应激障碍和相关症状的测量，以及恐惧习得和 表情。MGlu2/3激动剂甲硫氨蝶呤对症状的鉴别疗效评价 组成理论驱动和经验支持的创伤后应激障碍五因素表型模型的集群 症状将提供关于该药物如何不同地调节独特的维度的更大的特异性 创伤后应激障碍表型。MGlu2/3受体激动剂对应激性去甲肾上腺素的抑制作用 分泌，我们预测甲硫胺将在缓解焦虑方面有最显著的效果。 唤醒症状。！

The glutamatergic system plays a role in certain common behavioral manifestations of posttraumatic stress disorder (PTSD), e.g. mechanisms of fear learning and anxious arousal. We propose to evaluate the efficacy of the mGlu2/3 receptor agonist pomaglumetad methionil in treating PTSD in a randomized, double-blind, placebo-controlled, phase II clinical trial. Key endpoints of this trial include structured diagnostic and self- report measures of PTSD and related symptomatology, as well as objective biomarkers of fear acquisition and expression. Evaluation of the differential efficacy of the mGlu2/3 agonist pomaglumetad methionil on symptom clusters that comprise the theory-driven and empirically-supported five-factor phenotypic model of PTSD symptoms will provide greater specificity regarding how this drug differentially modulates unique dimensions of the PTSD phenotype. Given the inhibitory effects of mGlu2/3 receptor agonists on stress-induced NE secretion, we predict that pomaglumetad methionil will have the most pronounced effect in mitigating anxious arousal symptoms.!